Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Lymphoproliferative Disorder, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic/Myeloproliferative Neoplasms, Myelodysplastic Syndromes, Neurotoxicity, Pain, Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Brief summary
RATIONALE: Baclofen-amitriptyline-ketamine (BAK) gel may lessen peripheral neuropathy caused by chemotherapy. It is not yet known whether BAK gel is more effective than a placebo in treating peripheral neuropathy caused by chemotherapy . PURPOSE: This randomized phase III trial is studying BAK gel to see how well it works compared with a placebo in treating peripheral neuropathy caused by chemotherapy in patients with cancer.
Detailed description
OBJECTIVES Primary * Compare the effectiveness of baclofen-amitriptyline hydrochloride-ketamine (BAK) gel versus placebo, in terms of improving sensory neuropathy, in cancer patients with chemotherapy-induced peripheral neuropathy\> Secondary\> * Compare motor and autonomic symptoms and functioning, mood states, pain, and peripheral neuropathy in these patients. * Assess the adverse event profile of topical BAK gel. * Explore whether topical BAK gel is absorbed systemically. OUTLINE: Patients are stratified according to neurotoxic chemotherapy (active vs non-active), current use of opioids or oral pain medications (yes vs no), pain rating (4-7 vs 8-10), and prior ineffective pharmacologic treatment for peripheral neuropathy (yes vs no). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. * Arm II: Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Some patients in both arms may choose to continue on the active gel or, if on placebo, begin the active gel for an additional 8 weeks off study. Patients complete health, pain, mood, and quality of life questionnaires at baseline and periodically during study. Patients also record adverse symptoms weekly in a Symptom Experience Diary.
Interventions
DRUGbaclofen/amitriptyline/ketamine gel
Applied topically
OTHERplacebo
Applied topically
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS:\> * Diagnosis of cancer\> * Received or currently receiving neurotoxic chemotherapy including, but not limited to, taxanes (e.g., paclitaxel or docetaxel); platinum-based compounds (e.g., carboplatin, cisplatin, or oxaliplatin); vinca alkaloids (e.g., vincristine or vinblastine); or other neurotoxic chemotherapy agents (e.g., bortezomib, lenalidomide, or thalidomide)\> * Must have pain or symptoms of peripheral neuropathy attributable to chemotherapy for ≥ 1 month\> * Neuropathy is limited to either hands and/or feet where gel can be applied\> * Neuropathic pain score of ≥ 4 out of 10 on the numbness/tingling/pain numeric analogue scale\> * No pre-existing or history of peripheral neuropathy due to any cause other than chemotherapy (e.g., diabetes, alcohol, toxin, heredity)\> PATIENT CHARACTERISTICS:\> * ECOG performance status 0-2\> * Life expectancy ≥ 4 months\> * Creatinine ≤ 1.5 times upper limit of normal\> * Not pregnant or nursing\> * No ability to bear children defined by 1 of the criteria:\> * Menopausal (12 months and no menstrual period if natural menopause)\> * Underwent a hysterectomy and/or oophorectomy\> * Permanent surgical sterilization (tubal ligation)\> * Fertile patients must use effective contraception\> * Able to complete questionnaires independently or with assistance\> * Able to sign informed consent and understand the nature of a placebo-controlled trial\> * No history of an allergic reaction to baclofen, amitriptyline hydrochloride, and/or ketamine\> * No diagnosis of any New York Heart Association class I-IV congestive heart failure\> * No diagnosis of coronary artery disease including, but not limited to, myocardial infarction, within the past 5 years\> * No other medical condition that, in the opinion of the treating physician or allied health professional, would make this clinical trial unreasonably hazardous for the patient\> * No skin abnormalities at the intended application sites (hands and feet) of study gel (i.e., skin breakdown)\> PRIOR CONCURRENT THERAPY:\> * See Disease Characteristics\> * More than 30 days since prior anticonvulsants, tricyclic antidepressants, monoamine oxidase inhibitor, or other neuropathic pain medication (e.g., carbamazepine, phenytoin, valproic acid, gabapentin, lamotrigine, topical lidocaine patch or gel, capsaicin cream, or amifostine)\> \- Patients treated with any of these agents for peripheral neuropathy for ≤ 1 week during the past 30 days are eligible provided they are no longer taking the agent\> * More than 5 years since prior percutaneous transluminal coronary angioplasty or coronary artery bypass graft\> \- Prior heart valve replacement surgery allowed provided patient has fully recovered from the surgery\> * No concurrent use of study agents other than as specified in the trial\>
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Sensory Neuropathy as Measured by the European Organization for Research and Treatment of Cancer [EORTC] Quality of Life [QLQ] - Chemo-induced Peripheral Neuropathy [CIPN20] | From baseline to 4 weeks | The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The primary analysis was the change in sensory neuropathy subscale of the CIPN-20 from baseline to week 4. The area under the curve (AUC) from baseline to week 4 was calculated for each patient's sensory neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Autonomic Symptoms and Functioning as Measured by the EORTC QLQ-CIPN20 at Baseline and Week 4 | Up to 4 weeks | The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The secondary analysis was to compare changes from baseline at 4 weeks for the autonomic neuropathy subscale of the CIPN-20. To analyze this endpoint, the area under the curve (AUC) from baseline to week 4 was calculated for each patient's motor neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test. |
| Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS) | At 4 weeks | Each mood scale (0 - 100, higher is better mood) will be analyzed as an endpoint along with the total mood disturbance score. |
| Motor Neuropathy as Measured by the EORTC QLQ-CIPN20 at Baseline and Week 4 | From Baseline to week 4 | The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The secondary analysis was to compare changes from baseline at 4 weeks for the motor neuropathy subscale of the CIPN-20. To analyze this endpoint, the area under the curve (AUC) from baseline to week 4 was calculated for each patient's motor neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test. |
| Numbness, Tingling, and Pain as Measured by the Peripheral Neuropathy Questionnaire at Baseline and Weekly for 4 Weeks | Up to 4 weeks | The Peripheral Neuropathy Questionnaire was used to analyze this endpoint. Patient neuropathy symptoms were scored on a 0 - 100 scale (higher score represents less symptomatic). The area under the curve (AUC) from baseline to week 4 was calculated for each patient's score. The average AUC for the placebo arm and the topical amitriptyline HCl/ baclofen/ ketamine arm are reported. |
| Adverse Event Profile of Topical Amitriptyline HCl/ Baclofen/Ketamine > Frequency and Severity of Adverse Events Reported by the Patient in the > Symptom Experience Diary and Evaluated Through Clinical Assessment by NCI CTCAE v3.0 | Up to 4 weeks | Frequency and severity of adverse events reported by patients in weekly diary and evaluated through clinical assessment by NCI CTCAE v3.0. The number of patients reporting grade 3 or higher events are reported in this outcome measure. For a full list of all events, please refer to the Adverse Events section of this report. |
| Pain Severity and Interference as Measured by the Brief Pain Inventory (BPI) at Baseline and Week 4 | Up to 4 weeks | Pain severity, defined by the four items addressing worst, least, and average pain and pain right now as measured by the BPI will be analyzed identical to the primary endpoint. Additionally, total pain interference as measured by the BPI will be transformed onto a 0-100 ( higher is less pain) point scale. The area under the curve (AUC) from baseline to week 4 was calculated for each patient's score. The average AUC for the placebo arm and the topical amitriptyline HCl/ baclofen/ ketamine arm are reported. |
Countries
United States
Participant flow
Pre-assignment details
Two-hundred eight patients were enrolled to this study. Five patients cancelled prior to initiating protocol treatment and were therefore this study was analyzed using 203 remaining patients.
Participants by arm
| Arm | Count |
|---|---|
| Baclofen-amitriptyline Hydrochloride-ketamine Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically. | 101 |
| Placebo Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically | 102 |
| Total | 203 |
Baseline characteristics
| Characteristic | Baclofen-amitriptyline Hydrochloride-ketamine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 59.5 years | 62 years | 61 years |
| Region of Enrollment United States | 101 participants | 102 participants | 203 participants |
| Sex: Female, Male Female | 66 Participants | 60 Participants | 126 Participants |
| Sex: Female, Male Male | 35 Participants | 42 Participants | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 48 / 101 | 45 / 102 |
| serious Total, serious adverse events | 1 / 101 | 1 / 102 |
Outcome results
Primary
Total Sensory Neuropathy as Measured by the European Organization for Research and Treatment of Cancer [EORTC] Quality of Life [QLQ] - Chemo-induced Peripheral Neuropathy [CIPN20]
The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The primary analysis was the change in sensory neuropathy subscale of the CIPN-20 from baseline to week 4. The area under the curve (AUC) from baseline to week 4 was calculated for each patient's sensory neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test.
Time frame: From baseline to 4 weeks
Population: There were 26 participants in the BAK arm and 27 in the placebo arm who did not provide primary endpoint data. In the BAK arm, 11 refused due to experiencing an adverse event and 15 refused for non-specified reasons. In the placebo arm, eight refused due to an adverse event, one patient died, and 18 refused for non-specified reasons.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baclofen-amitriptyline Hydrochloride-ketamine | Total Sensory Neuropathy as Measured by the European Organization for Research and Treatment of Cancer [EORTC] Quality of Life [QLQ] - Chemo-induced Peripheral Neuropathy [CIPN20] | 61.0 (units on a scale) * week | Standard Deviation 16.22 |
| Placebo | Total Sensory Neuropathy as Measured by the European Organization for Research and Treatment of Cancer [EORTC] Quality of Life [QLQ] - Chemo-induced Peripheral Neuropathy [CIPN20] | 60.9 (units on a scale) * week | Standard Deviation 17.9 |
p-value: 0.9Wilcoxon (Mann-Whitney)
Secondary
Adverse Event Profile of Topical Amitriptyline HCl/ Baclofen/Ketamine > Frequency and Severity of Adverse Events Reported by the Patient in the > Symptom Experience Diary and Evaluated Through Clinical Assessment by NCI CTCAE v3.0
Frequency and severity of adverse events reported by patients in weekly diary and evaluated through clinical assessment by NCI CTCAE v3.0. The number of patients reporting grade 3 or higher events are reported in this outcome measure. For a full list of all events, please refer to the Adverse Events section of this report.
Time frame: Up to 4 weeks
Population: All patients that were assessed for adverse events are used in this analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Baclofen-amitriptyline Hydrochloride-ketamine | Adverse Event Profile of Topical Amitriptyline HCl/ Baclofen/Ketamine > Frequency and Severity of Adverse Events Reported by the Patient in the > Symptom Experience Diary and Evaluated Through Clinical Assessment by NCI CTCAE v3.0 | Grade 4+ Adverse Event | 1 Participants |
| Baclofen-amitriptyline Hydrochloride-ketamine | Adverse Event Profile of Topical Amitriptyline HCl/ Baclofen/Ketamine > Frequency and Severity of Adverse Events Reported by the Patient in the > Symptom Experience Diary and Evaluated Through Clinical Assessment by NCI CTCAE v3.0 | Grade 3+ Adverse Event | 8 Participants |
| Placebo | Adverse Event Profile of Topical Amitriptyline HCl/ Baclofen/Ketamine > Frequency and Severity of Adverse Events Reported by the Patient in the > Symptom Experience Diary and Evaluated Through Clinical Assessment by NCI CTCAE v3.0 | Grade 3+ Adverse Event | 5 Participants |
| Placebo | Adverse Event Profile of Topical Amitriptyline HCl/ Baclofen/Ketamine > Frequency and Severity of Adverse Events Reported by the Patient in the > Symptom Experience Diary and Evaluated Through Clinical Assessment by NCI CTCAE v3.0 | Grade 4+ Adverse Event | 1 Participants |
Secondary
Autonomic Symptoms and Functioning as Measured by the EORTC QLQ-CIPN20 at Baseline and Week 4
The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The secondary analysis was to compare changes from baseline at 4 weeks for the autonomic neuropathy subscale of the CIPN-20. To analyze this endpoint, the area under the curve (AUC) from baseline to week 4 was calculated for each patient's motor neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test.
Time frame: Up to 4 weeks
Population: There were 26 participants in the BAK arm and 27 in the placebo arm who did not provide primary endpoint data. In the BAK arm, 11 refused due to experiencing an adverse event and 15 refused for non-specified reasons. In the placebo arm, eight refused due to an adverse event, one patient died, and 18 refused for non-specified reasons.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baclofen-amitriptyline Hydrochloride-ketamine | Autonomic Symptoms and Functioning as Measured by the EORTC QLQ-CIPN20 at Baseline and Week 4 | 85.0 (units on a scale)*week | Standard Deviation 15.47 |
| Placebo | Autonomic Symptoms and Functioning as Measured by the EORTC QLQ-CIPN20 at Baseline and Week 4 | 86.8 (units on a scale)*week | Standard Deviation 15.03 |
p-value: 0.5Wilcoxon (Mann-Whitney)
Secondary
Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS)
Each mood scale (0 - 100, higher is better mood) will be analyzed as an endpoint along with the total mood disturbance score.
Time frame: At 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baclofen-amitriptyline Hydrochloride-ketamine | Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS) | POMS Anger-Hostility Score | 87.8 units on a scale | Standard Deviation 14.48 |
| Baclofen-amitriptyline Hydrochloride-ketamine | Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS) | POMS Depression-Dejection Score | 86.4 units on a scale | Standard Deviation 16.09 |
| Baclofen-amitriptyline Hydrochloride-ketamine | Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS) | POMS Tension-Anxiety Subscale | 83.2 units on a scale | Standard Deviation 17.09 |
| Baclofen-amitriptyline Hydrochloride-ketamine | Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS) | POMS VA Subscale | 31.1 units on a scale | Standard Deviation 18.42 |
| Baclofen-amitriptyline Hydrochloride-ketamine | Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS) | POMS Confusion-Bewilderment | 76.9 units on a scale | Standard Deviation 17.58 |
| Baclofen-amitriptyline Hydrochloride-ketamine | Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS) | POMS Fatigue-Inertia Score | 67.2 units on a scale | Standard Deviation 21.69 |
| Baclofen-amitriptyline Hydrochloride-ketamine | Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS) | Mean POMS Score | 71.5 units on a scale | Standard Deviation 13.27 |
| Placebo | Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS) | Mean POMS Score | 71.8 units on a scale | Standard Deviation 13.14 |
| Placebo | Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS) | POMS Anger-Hostility Score | 87.7 units on a scale | Standard Deviation 12.98 |
| Placebo | Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS) | POMS Confusion-Bewilderment | 77.9 units on a scale | Standard Deviation 11.75 |
| Placebo | Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS) | POMS VA Subscale | 33.0 units on a scale | Standard Deviation 19.61 |
| Placebo | Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS) | POMS Depression-Dejection Score | 85.8 units on a scale | Standard Deviation 15.23 |
| Placebo | Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS) | POMS Fatigue-Inertia Score | 63.6 units on a scale | Standard Deviation 22.22 |
| Placebo | Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS) | POMS Tension-Anxiety Subscale | 83.0 units on a scale | Standard Deviation 15.73 |
Secondary
Motor Neuropathy as Measured by the EORTC QLQ-CIPN20 at Baseline and Week 4
The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The secondary analysis was to compare changes from baseline at 4 weeks for the motor neuropathy subscale of the CIPN-20. To analyze this endpoint, the area under the curve (AUC) from baseline to week 4 was calculated for each patient's motor neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test.
Time frame: From Baseline to week 4
Population: There were 26 participants in the BAK arm and 27 in the placebo arm who did not provide primary endpoint data. In the BAK arm, 11 refused due to experiencing an adverse\> event and 15 refused for non-specified reasons. In the placebo arm, eight refused due to an\> adverse event, one patient died, and 18 refused for non-specified reasons.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baclofen-amitriptyline Hydrochloride-ketamine | Motor Neuropathy as Measured by the EORTC QLQ-CIPN20 at Baseline and Week 4 | 69.2 (units on a scale)* week | Standard Deviation 17.15 |
| Placebo | Motor Neuropathy as Measured by the EORTC QLQ-CIPN20 at Baseline and Week 4 | 70.1 (units on a scale)* week | Standard Deviation 19.48 |
p-value: 0.5Wilcoxon (Mann-Whitney)
Secondary
Numbness, Tingling, and Pain as Measured by the Peripheral Neuropathy Questionnaire at Baseline and Weekly for 4 Weeks
The Peripheral Neuropathy Questionnaire was used to analyze this endpoint. Patient neuropathy symptoms were scored on a 0 - 100 scale (higher score represents less symptomatic). The area under the curve (AUC) from baseline to week 4 was calculated for each patient's score. The average AUC for the placebo arm and the topical amitriptyline HCl/ baclofen/ ketamine arm are reported.
Time frame: Up to 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baclofen-amitriptyline Hydrochloride-ketamine | Numbness, Tingling, and Pain as Measured by the Peripheral Neuropathy Questionnaire at Baseline and Weekly for 4 Weeks | 172.6 units on a scale * week | Standard Deviation 82.09 |
| Placebo | Numbness, Tingling, and Pain as Measured by the Peripheral Neuropathy Questionnaire at Baseline and Weekly for 4 Weeks | 175.7 units on a scale * week | Standard Deviation 85.38 |
Secondary
Pain Severity and Interference as Measured by the Brief Pain Inventory (BPI) at Baseline and Week 4
Pain severity, defined by the four items addressing worst, least, and average pain and pain right now as measured by the BPI will be analyzed identical to the primary endpoint. Additionally, total pain interference as measured by the BPI will be transformed onto a 0-100 ( higher is less pain) point scale. The area under the curve (AUC) from baseline to week 4 was calculated for each patient's score. The average AUC for the placebo arm and the topical amitriptyline HCl/ baclofen/ ketamine arm are reported.
Time frame: Up to 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baclofen-amitriptyline Hydrochloride-ketamine | Pain Severity and Interference as Measured by the Brief Pain Inventory (BPI) at Baseline and Week 4 | Worst Pain | 58.1 units on a scale * week | Standard Deviation 25.48 |
| Baclofen-amitriptyline Hydrochloride-ketamine | Pain Severity and Interference as Measured by the Brief Pain Inventory (BPI) at Baseline and Week 4 | Least Pain | 78.0 units on a scale * week | Standard Deviation 20.28 |
| Baclofen-amitriptyline Hydrochloride-ketamine | Pain Severity and Interference as Measured by the Brief Pain Inventory (BPI) at Baseline and Week 4 | Average Pain | 66.4 units on a scale * week | Standard Deviation 21.99 |
| Baclofen-amitriptyline Hydrochloride-ketamine | Pain Severity and Interference as Measured by the Brief Pain Inventory (BPI) at Baseline and Week 4 | BPI Total Interference | 76.5 units on a scale * week | Standard Deviation 20.16 |
| Placebo | Pain Severity and Interference as Measured by the Brief Pain Inventory (BPI) at Baseline and Week 4 | BPI Total Interference | 77.3 units on a scale * week | Standard Deviation 21.16 |
| Placebo | Pain Severity and Interference as Measured by the Brief Pain Inventory (BPI) at Baseline and Week 4 | Worst Pain | 58.7 units on a scale * week | Standard Deviation 27.39 |
| Placebo | Pain Severity and Interference as Measured by the Brief Pain Inventory (BPI) at Baseline and Week 4 | Average Pain | 65.4 units on a scale * week | Standard Deviation 24.55 |
| Placebo | Pain Severity and Interference as Measured by the Brief Pain Inventory (BPI) at Baseline and Week 4 | Least Pain | 77.3 units on a scale * week | Standard Deviation 22.01 |